title: Vascular biomechanical properties in mice with smooth muscle specific deletion of Ndst1.
abstract: Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sulfation pattern of the heparan sulfate chains is a critical regulatory step affecting the binding of chemokines and growth factors. N-deacetylase-N-sulfotransferase1 (Ndst1) is one of the first enzymes to catalyze sulfation. Previously published work has shown that HSPGs alter tangent moduli and stiffness of tissues and cells. We hypothesized that loss of Ndst1 in smooth muscle would lead to significant changes in heparan sulfate modification and the elastic properties of arteries. In line with this hypothesis, the axial tangent modulus was significantly decreased in aorta from mice lacking Ndst1 in smooth muscle (SM22αcre(+)Ndst1(-/-), p < 0.05, n = 5). The decrease in axial tangent modulus was associated with a significant switch in myosin and actin types and isoforms expressed in aorta and isolated aortic vascular smooth muscle cells. In contrast, no changes were found in the compliance of smaller thoracodorsal arteries of SM22αcre(+)Ndst1(-/-) mice. In summary, the major findings of this study were that targeted ablation of Ndst1 in smooth muscle cells results in altered biomechanical properties of aorta and differential expression of myosin and actin types and isoforms.
authors.affiliation: Lillehei Heart Institute, Department of Medicine, University of Minnesota, 4-106 NHH, 312 Church St. SE, Minneapolis, MN, 55455, USA.
authors.forename: Neeta
authors.initials: N
authors.lastname: Adhikari
authors.forename: Marie
authors.initials: M
authors.lastname: Billaud
authors.forename: Marjorie
authors.initials: M
authors.lastname: Carlson
authors.forename: Spencer P
authors.initials: SP
authors.lastname: Lake
authors.forename: Kim Ramil C
authors.initials: KR
authors.lastname: Montaniel
authors.forename: Rod
authors.initials: R
authors.lastname: Staggs
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.forename: Dinesha
authors.initials: D
authors.lastname: Walek
authors.forename: Snider
authors.initials: S
authors.lastname: Desir
authors.forename: Brant E
authors.initials: BE
authors.lastname: Isakson
authors.forename: Victor H
authors.initials: VH
authors.lastname: Barocas
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hall
mesh_terms: D000818:Animals; D001158:Arteries / Q000503:physiopathology; D001696:Biomechanical Phenomena; D003187:Compliance; D015536:Down-Regulation / Q000235:genetics; D017353:Gene Deletion; D066298:In Vitro Techniques; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D015203:Reproducibility of Results; D013194:Staining and Labeling; D013314:Stress, Mechanical; D015238:Sulfotransferases / Q000172:deficiency* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014661:Vasoconstriction
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; C058992:Tagln protein, mouse; D015238:Sulfotransferases; C021350:heparitin sulfotransferase